| Autor: |
Sreenivasulu Godesi, Jeong-Ran Han, Jang-Keun Kim, Dong-Ik Kwak, Joohan Lee, Hossam Nada, Minkyoung Kim, Hyun-A Yang, Joo-Young Im, Hyun Seung Ban, Chang Hoon Lee, Yongseok Choi, Misun Won, Kyeong Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Pharmaceuticals, Vol 16, Iss 5, p 683 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1424-8247 |
| DOI: |
10.3390/ph16050683 |
| Popis: |
MDH1 and MDH2 enzymes play an important role in the survival of lung cancer. In this study, a novel series of dual MDH1/2 inhibitors for lung cancer was rationally designed and synthesized, and their SAR was carefully investigated. Among the tested compounds, compound 50 containing a piperidine ring displayed an improved growth inhibition of A549 and H460 lung cancer cell lines compared with LW1497. Compound 50 reduced the total ATP content in A549 cells in a dose-dependent manner; it also significantly suppressed the accumulation of hypoxia-inducible factor 1-alpha (HIF-1α) and the expression of HIF-1α target genes such as GLUT1 and pyruvate dehydrogenase kinase 1 (PDK1) in a dose-dependent manner. Furthermore, compound 50 inhibited HIF-1α-regulated CD73 expression under hypoxia in A549 lung cancer cells. Collectively, these results indicate that compound 50 may pave the way for the development of next-generation dual MDH1/2 inhibitors to target lung cancer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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